In the immature human brain, periventricular leukomalacia (PVL) is the predominant white matter injury underlying the development of cerebral palsy. PVL has its peak incidence during a well-defined period in human brain development (23-32 weeks postconceptional age) characterized by extensive oligodendrocyte migration and maturation. We hypothesized that the dramatic rise of oxygen tissue tension associated with mammalian birth and additional oxygen exposure of the preterm infant during intensive care may be harmful to immature oligodendrocytes (OLs). We therefore investigated the effects of hyperoxia on rat oligodendroglia cells in vitro and in vivo. Immature OLs (OLN-93), their progenitors [preoligodendrocytes (pre-OL)], and mature OLs were subjected to 80% hyperoxia (24-96 hr). Flow cytometry was used to assess cell death. Cell viability was measured by metabolism of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT). In addition, 6-day-old rat pups were subjected to 80% oxygen (24 hr) and then sacrificed, and their brains were processed for immunfluorescence staining. Apoptosis was detected at various stages (annexin-V, activated caspase-3) after 24-48 hr of incubation in 80% oxygen in pre- and immature OLs. Mature OLs were resistant to oxygen exposure. These results were confirmed by MTT assay. This cell death was blocked by administration of the pan-caspase inhibitor zVAD-fmk. Degeneration of OLs was confirmed in 7-day-old rat brains by positive staining for activated caspase-3. Hyperoxia triggers maturation-dependent apoptosis in immature and pre-OLs and involves caspase activation. This mechanism may be relevant to the white matter injury observed in infants born preterm.
Aim
Children and adolescents with end‐stage renal disease face a high morbidity and mortality. Palliative care provides a multidisciplinary approach to reduce disease burden and improve quality of life. This study evaluated concepts and current structures of palliative care from the perspective of a multidisciplinary paediatric nephrology team including physicians, nurses and psychosocial health professionals.
Methods
Evaluation was done by an online survey sent to the members of the German Society of Nephrology and to the nurse managers of German paediatric dialysis centres between April 9, 2018 and May 31, 2018.
Results
Out of the 52 respondents, 54% were physicians, 21% nurses and 25% psychosocial health professionals. The quality of actual palliative care service was rated as moderate (3.3 on a scale from one to six). Specialised palliative care teams (54%) and the caring paediatric nephrologist (50%) were considered as primarily responsible for palliative care. Two thirds wished for training in palliative care. In only 15% of the respondents’ centres, palliative care specialisation existed.
Conclusion
Palliative care structures in paediatric nephrology were not sufficient in the view of the multidisciplinary healthcare team. Therefore, efforts should be taken to integrate palliative care into the routine treatment of children and adolescents with chronic kidney diseases.
Our results indicate differential effects of ibuprofen and indomethacin on the expression levels of the vascular endothelial growth factor system in ductus arteriosus endothelial cells. In addition, vessel-specific differences between ductal and aortic endothelial cells were found. Further in vivo studies are needed to elucidate the biological significance of these findings.
The present data underline the contribution of radical forming processes to the pathogenesis of inner ear diseases. For experimental research, it is important to note that organotypic culture may be coupled with hypoxia.
Background: We aimed to develop a contrast agent suitable for targeting to E-selectin expressed on activated vascular endothelium in an in vivo model of inflammation and detection by magnetic resonance (MR) imaging.Methods: Anti-murine E-selectin F(ab')2 monoclonal antibody (mAb) (MES-1) was conjugated with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO). Flow cytometry, PERL staining for iron, and MR imaging were performed using CHO cells expressing mouse E-selectin (CHO-E) to detect binding of the conjugate in vitro, and a mouse model of contact hypersensitivity to oxazolone in the ear was used to investigate the in vivo characteristics of the MES-1-USPIO, with serial imaging being performed using an Oxford/Varian 9.4T MR imaging system with a custom receive-only coil. Tissue sections were stained to define the distribution of E-selectin expression and the localisation of the MES-1-USPIO conjugate.Results: The MES-1-USPIO was shown to bind to CHO-E in vitro. Following injection of MES-1-USPIO in vivo, distinct changes in the R2 relaxation rate (1/T2) characteristics could be detected in inflamed ears compared to controls. Histological analysis confirmed the vascular endothelial distribution of the MES-1-USPIO.Conclusions: E-selectin expression in vivo can be selectively and directly imaged non-invasively with magnetic resonance. This molecular imaging tool has the potential to be useful for the diagnosis and monitoring of early or occult inflammation, and may provide an attractive alternative to established clinical investigations such as the use of radiolabelled leukocytes. In addition, such an agent may have value in the investigation of some solid tumours and metastases, either by targeting tumour-associated neovasculature or tumour cells expressing E-selectin.
REGIONAL CEREBRAL BLOOD FLOW IN ASPHYCTIC FOETAL LAMBS AFTER RESCUE WITH MGSO4
DEPT. OF PAEDIATRICS OF CRUCES HOSPITAL (SPAIN)Background: Hypoxic-ischemic (HI) injury induced by partial cord clamping produces brain damage. MgSO4 infusion has been used as a neuroprotector, but it produces haemodynamic and cardiac changes.
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